treatment of anemia in patients with very low, low or intermediate risk myelodysplastic syndromes with ca-4948

Conditions: Myelodysplastic Syndromes; Anemia

Summary: anemia in lr-mds patients

anemia in non-transfusion dependent (ntd) or transfusion dependent (low or high transfusion burden, ltb/htb) patients with very low, low or intermediate risk myelodysplastic syndromes

Eligibility criteria:
inclusion criteria: 1. diagnosis of de novo myelodysplastic syndrome (mds) or de novo myelodysplastic/myeloproliferative neoplasias (mds/mpn) including mds/mpn-rs-t, mds/mpnu, acml or cmml 2. very low/low/intermediate risk disease: ipss-r up to 3.5 for mds; mds/mpn \< 10% bone marrow blasts; for cmml low or intermediate risk according to cpss-score 3. symptomatic anemia (based on valid and complete hemoglobin and transfusion history): * ntd (non transfusion dependent): \< 3 rbc transfusions and mean hemoglobin level \<10 g/dl within the last 16 weeks * ltb (low transfusion burden): 3-7 rbc transfusions within the last 16 weeks in at least two transfusion episodes, maximum 3 in 8 weeks * htb (high transfusion burden): ≥ 8 rbc transfusions within the last 16 weeks, ≥ 4 in 8 weeks 4. defined transfusion strategy 5. no available option of an approved mds therapy and classification of prior erythropoiesis-stimulating agent (esa) treatment as follows: * cohort a: esa exposed (and refractory or intolerant) * cohort b: esa naive and serum erythropoietin level \>200 u/l exclusion criteria: compliance with major study procedures * inability to swallow and retain oral medications (\> 10 pills) * patient does not accept bone marrow sampling during screening and after the treatment * patient does not accept up to weekly peripheral blood sampling during screening and treatment safety * ecog performance status ≥ 3 * inacceptable organ function 1. serum creatinine \> 2 × uln or calculated creatinine clearance \< 30 ml/min 2. ast \> 2 × uln or alt \> 2 × uln 3. total bilirubin \> 2 × uln (exception \>3 × uln in patients with documented gilbert's syndrome) interfering treatments * prior treatment with azacitidine or decitabine * treatment with erythropoiesis stimulating agent (esa), g-csf, gm-csf, lenalidomide, luspatercept and/or another investigational drug or device up to 14 days before registration * treatment with iron chelation therapy 56 days before registration, except for subjects on a stable or decreasing dose for at least eight weeks prior to inclusion and during study treatment * major surgery within 28 days prior to registration concomitant diseases * known human immunodeficiency virus infection (hiv) * active infectious hepatitis (hbv or hcv) * hepatitis virus detectable within 6 months before registration in patients with a history of hepatitis * history of other invasive malignancy, unless definitively treated with curative intent, provided it is deemed to be at low risk for recurrence by the treating physician * presence of an acute or chronic toxicity resulting from prior anti-cancer therapy that has not resolved to grade ≤ 1 (except anemia and alopecia) * known allergy or hypersensitivity to any component of the formulation of ca-494824 * severe cardiovascular disease (e.g. myocardial infarction within 6 months registration, unstable angina within 6 months registration, nyha class iii or greater congestive heart failure, serious arrhythmias uncontrolled on treatment, clinically significant pericardial disease, known qtc abnormality \> 450 msec on ecg formal requirements * positive serum pregnancy test in women of childbearing potential * women of childbearing potential and men who partner with a woman of childbearing potential unwilling to use highly effective contraceptive methods for the duration of the study and for 90 days after the last dose of ca-4948 * age under 18 years at registration * inability to provide written informed consent * simultaneous participation in another interventional clinical trial or participation in any clinical trial involving administration of an investigational medicinal product within 28 days prior registration

Keywords: mds anemia myelodysplastic syndrome irak4